Impact of ApoB-100 expression on cognition and brain pathology in wild-type and hAPPsl mice

Tina Löffler, Stefanie Flunkert, Daniel Havas, Miklós Sántha, Birgit Hutter-Paier, Ernst Steyrer, Manfred Windisch

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

During their lifetime, people are commonly exposed to several vascular risk factors that may affect brain ageing and cognitive function. In the last few years, increasing evidence suggests that pathological plasma lipid profiles contribute to the pathogenesis of late-onset Alzheimer's disease. Importantly, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol values, that is, increased apolipoprotein B-100 (ApoB-100) levels, represents an independent risk factor. In this study, the effects of ApoB-100 overexpression, either alone or in combination with cerebral expression of human amyloid precursor protein (hAPP), on cognitive functions and brain pathology were assessed. Our results show that ApoB-100 overexpression induces memory decline and increases cerebral lipid peroxidation and amyloid beta levels compared to those in wild-type animals. Although double-transgenic ApoBxAPP animals did not develop more distinct behavioral deficits than single-transgenic hAPP littermates, hApoB-100 expression caused additional pathophysiological features, such as high LDL and low HDL-cholesterol levels, increased lipid peroxidation, and pronounced ApoB-100 accumulation in cerebral vessels. Thus, our results indicate that ApoBxAPP mice might better reflect the situation of elderly humans than hAPPsl overexpression alone.

Original languageEnglish
Pages (from-to)2379-2388
Number of pages10
JournalNeurobiology of Aging
Volume34
Issue number10
DOIs
Publication statusPublished - Oct 1 2013

Keywords

  • Alzheimer's disease
  • Apolipoprotein B-100
  • Brain
  • Hyperlipidemia
  • Transgenic mice
  • Vascular risk factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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